Intracranial pressure (ICP), and other intracranial hemodynamic parameters, are important for diagnosing a variety of medical conditions involving the central nervous system, and for monitoring their treatment. The most commonly used methods for measuring ICP are invasive, involving inserting a probe into the central nervous system space. Such methods can be dangerous, because they carry a risk of infection or hemorrhage, and they can be inaccurate. Inaccuracies can result from obstruction of the fluid in an external strain gauge, or from poor maintenance of a reference point with external transducers, or from calibration issues when fiberoptic devices are used.
Several patents and published applications, including US 2004/0049105 to Crutchfield et al, US 2006/0094964 to Ragauskas, U.S. Pat. No. 4,984,567 to Kageyama, U.S. Pat. No. 6,117,089 to Sinha, MXPA01011471 to Inta Medics, Ltd. (Israel), and U.S. Pat. No. 6,875,176, suggest the use of ultrasound to indirectly determine ICP in a non-invasive manner. A similar method using MRI is suggested by U.S. Pat. No. 6,245,027 to Alperin.
Although methods involving ultrasound and MRI are non-invasive, they require expensive equipment, and skilled personnel to interpret the results. Hence, they are not practical for continuous monitoring of ICP in patients.
U.S. Pat. No. 6,773,407 describes measuring ICP by temporarily raising it a known amount, and directly measuring the resulting increase in volume of the skull. EP0020677 describes temporarily occluding the jugular vein, and determining ICP by observing the response upstream. These methods may also not be practical for continuous monitoring of ICP, because they may cause some danger or discomfort to the patient.
There are methods of continuously monitoring ICP non-invasively. U.S. Pat. No. 7,041,063 describes an optical sensor mounted on the outside of the cornea, which can detect ICP by its effect on swelling of the retina and the optic nerve head. Russian patent publication RU2185091, to Zabolotskikh et al, describes measuring ICP non-invasively by measuring blood pressure in the central retinal vein. U.S. Pat. No. 6,976,963 uses periodic swelling of the external auditory canal, at the cardiac frequency, to measure the pulse waveform of the blood pressure, and uses that to infer, among other things, ICP. Russian patent publication RU2163090 to Bokhov et al measures ICP by measuring the mechanical tension in the tympanic membrane at auditory frequencies. U.S. Pat. No. 5,040,540 to Sackner describes a mechanical transducer on the neck, which non-invasively measures central venous blood pressure in infants, and uses that to infer ICP, using the known relation between central venous pressure and ICP. However, it is difficult to measure central venous pressure non-invasively in adults, without access to large veins.
U.S. Pat. No. 6,491,647 to Bridger et al describes a mechanical external (non-invasive) blood pressure sensor which can be used, among other uses, for assessing blood flow in the temples of patients with elevated ICP. Using this kind of mechanical blood pressure sensor is described as superior to using bio-impedance methods, or photoplethysmography, for measuring blood flow. Bridger et al does not describe methods of measuring ICP.
Rheoencephalography (REG) is a technique that uses bio-impedance measurements of the head to obtain information on about cerebral blood circulation and circulatory problems. Generally, changes in impedance Z across the head, for a particular arrangement of electrodes, are measured as a function of time t over a cardiac cycle, and sometimes over a breathing cycle, due to changes in the volume and distribution of blood in the head. As described by W. Traczewski et al, “The Role of Computerized Rheoencephalography in the Assessment of Normal Pressure Hydrocephalus,” J. Neurotrauma 22, 836-843 (2005), REG is commonly used to measure or diagnose problems with circulatory resistance, and problems with arterial elasticity. In patients with normal pressure hydrocephalus, for example, Traczewski et al find two different patterns in Z(t), depending on the elasticity of the small cerebral arteries. The pattern of Z(t) seen in a given patient can be used to make predictions about the likely outcome of different treatments for the hydrocephalus. These patients all had similar, normal values of ICP.
WO 06/006143 and WO 06/011128 to Shapira et al, and US 2005/0054939 and WO 03/059164 to Ben-Ari et al, describe the use of REG to monitor cerebral blood flow, for example in order to detect sudden decreases in cerebral blood flow rate. Specially designed electrodes, and supplementary information from photoplethysmography (PPG), are optionally used to make the bio-impedance measurements more sensitive to cerebral blood flow, and less sensitive to peripheral blood flow in the head. WO 03/059164 describes using the change in impedance of the head over a cardiac cycle as an indicator of cerebral blood flow. WO 06/011128 describes using the rate of change in impedance following the diastole as an indicator of cerebral blood flow.
J. Gronlund, J. Jalonen, and I. Valimaki, “Transcephalic electrical impedance provides a means for quantifying pulsatile cerebral blood volume changes following head-up tilt,” Early Human Development 47 (1997) 11-18, describe electrical impedance measurements of the head in premature newborn infants. Changes in impedance associated with the cardiac cycle are said to reflect changes in total cerebral blood volume, and earlier papers are referenced which are said to demonstrate this. Variability in impedance, in the range of 1.5 to 4 Hz, was found to decrease by 27%, on average, when the infants' heads were tilted up by 20 degrees.
Low cerebral blood flow is caused by low cerebral perfusion pressure (CPP), which is the difference between cranial intra arterial pressure (CIAP) and ICP. A low value of CPP may be due to either high ICP, or low CIAP. Low CIAP, in turn, may be due to 1) a systemic problem such as low mean arterial pressure (MAP), caused for example by a cardiac problem, or it may be due to 2) a blockage or hemorrhage of an artery in or leading to the head, resulting in a CIAP that is lower than the MAP. Monitoring MAP is a useful method for detecting the first set of conditions, but may not be useful for detecting the second set of conditions.
Czosnyka et al, J Neurosurg 1998; 88:802-8 describes the use of transcranial Doppler (TCD) ultrasound to estimate CPP non-invasively, but this technique is not practical to use for continuous monitoring.
Total cerebral blood volume (CBV) may be useful for diagnosing hemorrhagic strokes, and for diagnosing problems caused by traumatic brain injury. Positron emission tomography (PET) has been used to measure CBV. Wintermark et al, Stroke 2005; 36:e83-e99 describes the use of perfusion computed tomography (PCT) for measuring CBV. These techniques are also not practical for continuous monitoring of patients. It is known that changes in electrical impedance of the head are an indication of changes in cerebral blood volume; see, for example, Traczewski et al, cited above.
All of the patents and other publications cited above are incorporated herein by reference.